DOCSLIB.ORG

The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis Via Adhesive-Dependent and Adhesive-Independent Mechanisms

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis Via Adhesive-Dependent and Adhesive-Independent Mechanisms Research Article The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis via Adhesive-Dependent and Adhesive-Independent Mechanisms Madappa N. Kundranda,1 Melodie Henderson,3 Kathy J. Carter,3 Lee Gorden,3 Awadh Binhazim,2 Sanhita Ray,1 Trevor Baptiste,1 Masih Shokrani,1 Maria L. Leite-Browning,3 Willi Jahnen-Dechent,4 Lynn M. Matrisian,3 and Josiah Ochieng1,3 Departments of 1Biochemistry and 2Pathology, Meharry Medical College and 3Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, and 4IZKF BIOMAT, University Clinics, Aachen, Germany Abstract serum concentration drops after trauma, infection, and certain Fetuin-A is a serum glycoprotein in the cystatin family malignancies. Recently, a second protein of the fetuin family called associated with the regulation of soft tissue calcification. We fetuin-B was described in humans and rodents (1). Based on domain tested the role of systemic fetuin in tumor cell growth and homology, overall conservation of cysteine residues and chromo- metastasis by injecting Lewis lung carcinoma (LLC) cells into somal assignments of the corresponding genes in these species, fetuin-B was described as a paralogue of fetuin-A. fetuin-A null and their wild-type (WT) littermate control C57BL/6 mice via the tail vein, s.c., and intrasplenic routes. Fetuin-A has been linked to a number of cellular functions such In the experimental metastasis assay, the lungs of the WT as brain development (2), bone remodeling, and immune function (5, 6). It can also mimic and antagonize the anti-mitogenic effects mice were filled with metastatic nodules, whereas the lungs h of the fetuin-A null mutant mice were virtually free of of transforming growth factor- in test tube assays, in cell culture, colonies at the end of 2 weeks. Lung colonization responded and in intact animals (7, 8). Some of these functions however, can to the levels of serum fetuin-A in a dose-dependent manner, be attributed to a number of proteins, which copurify with fetuin- as observed by the formation of half as many colonies in As, and has therefore made it difficult to assign a particular mice heterozygous for the fetuin-A locus compared with function to fetuin-A without ambiguity (9). Fetuin-A deficiency in homozygous WT mice and restoration of lung colonization mice is associated with a mild soft tissue calcification phenotype by the administration of purified fetuin-A to fetuin-A-null (5). The ectopic calcification becomes dramatically exacerbated mice. Serum fetuin-A also influenced the growth of LLC cells when the fetuin-A deficiency is combined with the genetic injected s.c.: fetuin-A-null mice developed small s.c. tumors background DBA/2, which is sensitive to dystrophic calcification (10). These data prove that fetuin-A is a potent systemic inhibitor only after a substantial delay. Similarly, intrasplenic injection of LLC cells resulted in rapid colonization of the liver with of unwanted ectopic calcification. metastasis to the lungs within 2 weeks in the WT but not Fetuin-A, as the major constituent of bovine fetal serum, has long fetuin-A null mice. To examine the mechanism by which been suspected of being the active cell growth promoter in serum. fetuin-A influences LLC colonization and growth, we showed However, this assignment was challenged on the grounds that that LLC tumor cells adhere to fetuin-A in a Ca2+-dependent fetuin-A is a sticky molecule and thus the contaminating growth fashion, resulting in growth of the tumor cells. These studies factors that copurify with it are most likely responsible for the support the role of fetuin-A as a major growth promoter in growth stimulation (9). The availability of fetuin-A null mice has serum that can influence tumor establishment and growth. enabled us to revisit this problem in the present studies. We have examined the role of fetuin-A in the colonization of lungs and livers (Cancer Res 2005; 65(2): 499-506) of fetuin-A null C57BL/6 mice and their wild-type (WT) littermate controls by Lewis lung carcinoma (LLC) cells following tail vein and Introduction intrasplenic injections. We have also examined s.c. growth of LLC Fetuin-A is the bovine homologue of the human a 2HS glyco- cells in the fetuin-A null, heterozygous, and WT littermate controls. protein (Ahsg). The fetuin-A family encompasses a related group of We report that the lack of fetuin-A in these mice significantly glycoproteins synthesized by the liver and have been designated protects them from developing tumors in vivo. Furthermore, fetuin- fetuin in sheep, pig and cow, 63-kDa phosphoprotein in rat, and A is capable of promoting the growth of more aggressive tumor cells countertrypin in mouse (1). The serum concentration of the bovine but not benign and normal cells in vitro. The cells adhere and divide protein is high during fetal development f20 mg/mL but drops to on immobilized fetuin-A in the presence of 2 mmol/L Ca2+ ions. The a level of f0.60 mg/mL in the adult serum (2). The fetal levels in binding of fetuin-A to the surface of the cells triggers the PI3 kinase/ human (f1.5 mg/mL) is lower than in bovine and yet adult levels of Akt signaling pathway and cell proliferation. Ahsg in the blood of humans is comparable to the bovine blood levels at f0.50 mg/ mL. Ahsg/fetuin-A is a member of the cystatin family of proteins and is a negative acute phase protein (1, 3, 4) in that its Materials and Methods Animals. The strategies for producing fetuin-A null mutant mice were as described (5). The original null mutant strain 129,B6,Ahsgtm,Mbl was crossed to pure-bred C57BL/6 mice from a commercial breeder (Charles River, Requests for reprints: Josiah Ochieng, Meharry Medical College, Nashville, TN 37208. Phone: 615-327-6119; Fax: 615-327-6442; E-mail: [email protected]. Sulzfeld, Germany) for five successive generations resulting in the strain I2005 American Association for Cancer Research. B6,Ahsgtm1Wja according to Institute for Laboratory Animal Research www.aacrjournals.org 499 Cancer Res 2005; 65: (2). January 15, 2005 Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 2005 American Association for Cancer Research. Cancer Research nomenclature. Animals used in this study originated from sibling crosses of tumor growth monitored and measured for up to 7 weeks. The length and heterozygous offspring of the fifth back-cross (>99.9% pure C57BL/6 genetic width (in mm) of the tumors were measured by Verner Caliper and tumor background). Littermate homozygous B6,AhsgÀ/À and B6,Ahsg+/+ mice were volume determined as 0.5 Â width2 Â length. used. All animal experiments conformed to established procedures and were Adhesion of Cells to Fetuin-A–Coated Wells. Cells (4 Â 104 cells approved by the local animal experimentation review board. per well) were allowed to adhere to microtiter wells coated with 100 AL For genotyping during mouse breeding, DNA was obtained by proteinase of 0.5% fetuin-A or asialofetuin-A in serum-free medium in the absence and K digestion and extraction of tail biopsies taken at the time of weaning as presence of Ca2+ ions. After 1 to 2 hours of incubation, the nonadherent cells described. The identity of animals was confirmed by PCR analysis. WT– were washed off using the same medium and the adherent cells fixed with specific primers were Fet1: 5V-GAGACTGTGACTTCCACATCC-3V and Fet2: 5% glutaraldehyde in PBS followed by staining with crystal violet and pho- 5V-GGTTCCATTATTCTGTGTGTTG-3V, whereas the null mutant tographed. To the stained cells in the microtiter wells, 100 AL of 0.1 mol/L (knockout) primers were Neo1: 5V-ATCTCCTGTCATCTCACCTTGC-3V and acetic acid were added per well and the absorbance of the eluted stain was Neo2: 5V-ACCCCACCCCCACCCCCGTAGC-3V. The PCR conditions were recorded at 570 nm using a microplate reader MRX (Dynex Technologies). optimized at 95jC for 15 minutes for 1 cycle and then 94jC; 1 minute and Growth and Analysis of Cell Cycle of LLC in the Presence and Absence 57jC; 1 minute and 72jC; 1 minute for 4 cycles and lastly 91jC; 30 seconds of Fetuin-A. To the wells of a 96-well tissue culture microtiter plate, 2 Â 104 and 57jC; 30 seconds and 72jC; 30 seconds for 28 cycles. The product cells per well were added in DMEM/F12 (lacking Ca2+ and Mg2+ ions) (25 AL) was resolved on a 1.5% agarose gel. The WT product is a 500-bp containing 0.5% bovine fetuin-A (w/v) and 0.04 or 2 mmol/L CaCl2. As positive band, whereas a knockout product is 650 bp. control, cells were also allowed to grow in DMEM/F12 supplemented with Cell Culture. LLC is a spontaneously occurring lung cancer in C57BL/6 10% FBS (complete medium). Growth was measured every 24 hours for at mice. The tumor cell line was obtained from American Type Culture least 5 days. The number of viable cells was determined by the Alamar blue Collection (Rockville, MD) and is routinely maintained in DMEM medium assay (14, 15). In this assay reducing conditions, which reflect mitochondrial supplemented with 10% heat inactivated fetal bovine serum (FBS), 2 mmol/L activity turns the Alamar blue dye from blue to pink with increased glutamine, 100 Ag/mL streptomycin, and 100 IU/mL penicillin. Other cells fluorescence at 590 nm after excitation at 544 nm. Every 24 hours, Alamar blue used in the study were breast epithelial cell lines, BT-549, galectin-3 dye was added to the conditioned medium in the wells of microtiter plates at a transfected subclone of BT-549 named 11-9-1-4 (11–13), MDA-MB-231, and dilution of 1:20 and initial fluorescence taken using a luminescence ZR-75-1.
Load more

Recommended publications
  • Fetuin (␣2-HS-Glycoprotein) Opsonizes Cationic Macrophage- Deactivating Molecules (CNI-1493͞P38 Mitogen-Activated Protein Kinase)
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 14429–14434, November 1998 Medical Sciences Fetuin (a2-HS-glycoprotein) opsonizes cationic macrophage- deactivating molecules (CNI-1493yp38 mitogen-activated protein kinase) HAICHAO WANG*†‡,MINGHUANG ZHANG†,MARINA BIANCHI†,BARBARA SHERRY†,ANDREW SAMA*, AND KEVIN J. TRACEY†§ Departments of *Emergency Medicine and §Surgery, North Shore University Hospital-New York University School of Medicine, and †The Picower Institute for Medical Research, Manhasset, NY 11030 Communicated by George J. Todaro, University of Washington, Seattle, WA, September 22, 1998 (received for review February 5, 1998) ABSTRACT Macrophages become activated by bacterial of circulating fetuin, but it also is expressed by mono- endotoxin (lipopolysaccharide) and other stimuli to release cyteymacrophages (26). The fetuin promoter region has several proinflammatory cytokines and NO. To prevent release of toxic potential interleukin 6-responsive elements (27), and its synthesis or potentially lethal quantities of these factors, the state of is down-regulated during injury and inflammation (20). Fetuin is macrophage activation is counter-regulated by anti-inflamma- an acidic glycoprotein with three N-linked and three O-linked tory mediators (e.g., glucocorticoid hormones, interleukin 10, oligosaccharide chains, whose terminal sugar residues are rich in b and transforming growth factor type ). Fetuin, a negative sialic acid (N-acetylneuraminic acid), contributing to its net acute-phase protein, recently was implicated as an anti- negative charge (28). A role for fetuin as a carrier of bioactive inflammatory mediator, because it is required for macrophage molecules has been proposed based on observations that it binds deactivation by spermine. In the present studies, we found that and carries Ca21 ion (22).
    [Show full text]
  • New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 2 August 2021 doi:10.20944/preprints202108.0048.v1 Review New Metabolic and Genetic Biomarkers for Diagnosis of Ulcerative Colitis Elena-Emilia Tudoroiu1, Mihaela-Andreea Costache1 and Maria-Andreea Stancu 1,* and Anca Lucia Pop1 1 Department of Clinical Laboratory, Food Safety, "Carol Davila" University of Medicine and Pharmacy, 6 Traian Vuia Street, Bucharest 020945, Romania, [email protected], [email protected], [email protected], [email protected] * Correspondence: [email protected], (M.S.); [email protected] (A.L.P.) Tel.: +40745009910 Abstract: Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.
    [Show full text]
  • 2HS-Glycoprotein, an Antagonist of Transforming Growth Factor in Vivo
    [CANCER RESEARCH 64, 6402–6409, September 15, 2004] ␣2HS-glycoprotein, an Antagonist of Transforming Growth Factor ␤ In vivo, Inhibits Intestinal Tumor Progression Carol J. Swallow,1,2 Emily A. Partridge,1 Jennifer C. Macmillan,1 Tania Tajirian,1 Gianni M. DiGuglielmo,1 Kazy Hay,1 Melanie Szweras,1 Willi Jahnen-Dechent,3 Jeff L. Wrana,1,2 Mark Redston,1 Steven Gallinger,1,2 and James W. Dennis1,2 1Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; 2Departments of Molecular and Medical Genetics and Surgery, University of Toronto, Toronto, Ontario, Canada; and 3Interdisziplina¨ren Zentrums fu¨r Klinische Forschung BIOMAT, Klinikum der Rheinisch-Westfa¨lischen Technischen Hoschschule, Aachen, Aachen, Germany ABSTRACT ␤1-induced epithelial-mesenchymal transition is characterized by down-regulation of E-cadherin expression, loss of tight junctions, and ␤ Transforming growth factor (TGF)- 1 is associated with tumor pro- increased cell motility (1, 10) and is dependent on phosphatidylinosi- gression and resistance to chemotherapy in established cancers, as well as tol 3Ј-kinase/Akt activation (11), a key pathway promoting tumor cell host immune suppression. Here, we show that the serum glycoprotein ␣2-HS-glycoprotein (AHSG) blocks TGF-␤1 binding to cell surface re- invasiveness (12). Epithelial-mesenchymal transition appears to be a ceptors, suppresses TGF-␤ signal transduction, and inhibits TGF-␤- close in vitro correlate of metastatic capacity, and both require coop- induced epithelial-mesenchymal transition, suggesting that AHSG may erative signaling of TGF-␤ and Ras/mitogen-activated protein kinase play a role in tumor progression. In 66 consecutive sporadic human pathways (13, 14). Tumor-derived TGF-␤1 also has paracrine effects colorectal cancer specimens, we observed a 3-fold depletion of ASHG in on host cells that promote angiogenesis, alter matrix turnover, and tumor compared with normal tissue, whereas levels of other abundant suppress immune cell functions (1, 7, 15, 16).
    [Show full text]
  • Fetuin a Concentration in the Second Trimester Amniotic Fluid of Fetuses with Trisomy 21 Appears to Be Lower: Phenotypic Considerations
    Hindawi Publishing Corporation Mediators of Inflammation Volume 2012, Article ID 138971, 4 pages doi:10.1155/2012/138971 Research Article Fetuin A Concentration in the Second Trimester Amniotic Fluid of Fetuses with Trisomy 21 Appears to Be Lower: Phenotypic Considerations S. Iliodromiti,1, 2 N. Vrachnis,1 Evangelia Samoli,3 Z. Iliodromiti,1 C. Pangalos,4 N. Drakoulis,5 G. Creatsas,1 and D. Botsis1 1 2nd Department of Obstetrics and Gynecology, University of Athens Medical School, Aretaieion Hospital, 124B Vas. Sofias Avenue, 115 26 Athens, Greece 2 West of Scotland Deanery, Obstetrics and Gynaecology, Glasgow, G3 8BW, UK 3 Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, 115 27 Athens, Greece 4 Diagnostic Genetic Centre, 115 28 Athens, Greece 5 Department of Pharmaceutical Technology, School of Pharmacy, University of Athens, 157 71 Athens, Greece Correspondence should be addressed to N. Vrachnis, [email protected] Received 23 July 2011; Revised 21 November 2011; Accepted 21 November 2011 Academic Editor: Teresa Zelante Copyright © 2012 S. Iliodromiti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Objective. We investigated whether the concentration of the glycoprotein fetuin A is altered in the second trimester amniotic fluid of trisomy 21 pregnancies compared with euploid pregnancies. Methods. 25 pregnancies with an extra chromosome 21 were matched for maternal and gestational age with 25 pregnancies with normal karyotype. Levels of fetuin A in amniotic fluid were measured by a commercially available enzyme-linked immunosorbent assay (ELISA) kit.
    [Show full text]
  • Understanding the Effects of Fetuin-A in Pregnancy
    Central Medical Journal of Obstetrics and Gynecology Editorial *Corresponding author Luis M. Gómez, Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Tennessee Health Sciences Center, Memphis, TN, USA, Understanding the Effects of Email: [email protected] Submitted: 31 August 2013 Fetuin-A in Pregnancy Accepted: 31 August 2013 Published: 02 September 2013 Luis M. Gómez* Copyright Division of Maternal-Fetal Medicine, University of Tennessee Health Sciences Center, © 2013 Gómez USA OPEN ACCESS Human fetuin-A has emerged as a provocative molecule which actions in pregnancy have become the subject of research Women who present with preeclampsia are at risk of developing especially since the last decade. Also known as alpha-2 Heremans- metabolic syndrome later in their life [13,14]. Initial attempts Schmid glycoprotein, fetuin-A is a circulating glycoprotein to associate fetuin-A with preeclampsia were reported by produced in increased amounts during fetal life by various Shinagawa and Saitoh who found that fetuin-A was more tissues. Similar fetuin-A concentrations in maternal serum and prevalent among urine of women who developed preeclampsia umbilical cord suggest passive placental transfer of fetuin-A [15]; this association persisted after delivery. Park and during pregnancy [1]. The concentration of fetuin-A in plasma colleagues compared maternal serum proteome in women who decreases soon after delivery [2]. In the adult life, it is actively developed severe preeclampsia (n=8) with normal pregnancies secreted into the blood stream mainly by the liver [3]. Research (n=5) [16]; among candidate target proteins, fetuin-A was investigating the effects of fetuin-A in pregnancy has emerged noted to be elevated in severe preeclampsia cases.
    [Show full text]
  • Axial Spondyloarthritis and Inflammatory Bowel Disease
    Rheumatology International Rheumatology https://doi.org/10.1007/s00296-021-04940-1 INTERNATIONAL OBSERVATIONAL RESEARCH Axial spondyloarthritis and infammatory bowel disease: association between disease activity and endothelial dysfunction markers Hanna Przepiera‑Będzak1 · Katarzyna Fischer2 · Marek Brzosko1 Received: 25 May 2021 / Accepted: 28 June 2021 © The Author(s) 2021 Abstract Objective We aimed to assess patients with axial spondyloarthritis (axSpA) and infammatory bowel disease (IBD) for disease activity and serum markers of endothelial dysfunction. Methods We studied 161 patients (123 males, 38 females) with axSpA: 153 with ankylosing spondylitis and 8 with non- radiographic axSpA, and 30 healthy controls (HC). We collected: age; sex; disease duration; extra-articular symptoms (IBD and acute anterior uveitis), comorbidities; human leukocyte antigen B27 status; and treatment. We measured serum inter- leukin (IL)-6, interleukin-18, IL-23, vascular endothelial growth factor (VEGF) epidermal growth factor (EGF), asymmetric dimethylarginine (ADMA), endothelin-1 (ET-1), and fetuin-A levels. Results IBD was diagnosed in 19 (11.8%) patients with axSpA. Compared to patients with axSpA without IBD, those with IBD had higher serum C-reactive protein (CRP) level (p = 0.05), erythrocyte sedimentation rate (ESR) (p = 0.005), and serum ET-1 levels (p = 0.01). In patients with axSpA and IBD, ET-1 levels correlated positively with CRP level (p = 0.006) and ESR (p = 0.02), and ADMA levels with visual analog scale scores (p = 0.01). Patients with axSpA and IBD had higher serum levels of IL-6 (p = 0.01), IL-18 (p = 0.005), and ADMA (p = 0.01) and lower serum levels of fetuin-A (p = 0.01) than did controls.
    [Show full text]
  • Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects
    life Article Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects Hajnalka L˝orincz 1, Imre Csige 2,3, Mariann Harangi 1, Anita Szentpéteri 1, Ildikó Seres 1, Zoltán Szabó 2, György Paragh 1 and Sándor Somodi 1,2,* 1 Department of Internal Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; [email protected] (H.L.); [email protected] (M.H.); [email protected] (A.S.); [email protected] (I.S.); [email protected] (G.P.) 2 Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary; [email protected] (I.C.); [email protected] (Z.S.) 3 Doctoral School of Health Sciences, University of Debrecen, 4032 Debrecen, Hungary * Correspondence: [email protected] Abstract: Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atheroscle- rosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls 2 Citation: L˝orincz,H.; Csige, I.; (BMI: 24.5 ± 2.5 kg/m ) were enrolled in our study. Serum fetuin-A and RBP4 were measured by Harangi, M.; Szentpéteri, A.; Seres, I.; ELISA.
    [Show full text]
  • Proteinuria As the Most Relevant Parameter Affecting Fetuin-A Levels in Preeclampsia
    ACTA FACULTATIS MEDICAE NAISSENSIS UDC: 616.61-008.6 DOI: 10.1515/afmnai-2015-0027 Original article Proteinuria as the Most Relevant Parameter Affecting Fetuin-A Levels in Preeclampsia Hussein Kadhem Al-Hakeim, Roaa Ali Muhammed Ali Department of Chemistry, College of Science, University of Kufa, Iraq SUMMARY The present study aimed to examine the factors affecting the possible changes in serum fetuin-A in patients with preeclampsia (PE). The examined factors included the parameters of insulin resistance (IR) [(insulin sensitivity (HOMA%S), insulin resistance (HOMA2IR), and beta-cell functions (HOMA%B)], which were calculated using the HOMA2 calculator, and total and ionized calcium and magnesium levels. Sixty PE patients and thirty healthy pregnant women, which comprised the study group and control group, respectively participated in the present study. Fetuin-A, estradiol, insulin, glucose, total and ionized calcium and magnesium, total protein, albumin, and globulins were measured in their sera. The results of the present study showed that serum total and ionized magnesium and the I.Ca/Mg ratio decreased in PE women. Although the fasting insulin level and HOMA2IR were higher and HOMA2%S was lower in PE compared with the control women, PE did not appear as an overt insulin-resistant state. Serum fetuin-A was low in PE patients compared with the control group because PE women had proteinuria. Fetuin-A levels were not correlated with the characteristics and IR parameters, cations, and estradiol levels, but it was correlated with the severity of proteinuria. These results confirmed the hypothesis that proteinuria results in the loss of fetuin-A because it has a low molecular weight.
    [Show full text]
  • Review FETUIN-A – ALPHA2-HEREMANS
    J Biomed Clin Res Volume 11 Number 1, 2018 DOI: 10.2478/jbcr-2018-0002 Review FETUIN-A – ALPHA2-HEREMANS-SCHMID GLYCOPROTEIN: FROM STRUCTURE TO A NOVEL MARKER OF CHRONIC DISEASES PART 2. FETUIN-A – A MARKER OF INSULIN RESISTANCE AND RE- LATED CHRONIC DISEASES Regina S. Komsa-Penkova, Summary Katya S. Kovacheva1, Georgy M. Golemanov, Fetuin-A is a secretory liver glycoprotein with multiple Veselin P. Penkov2, physiological functions such as regulation of insulin 3 resistance, tissue calci¿ cation, bone metabolism, cellular Zdravka V. Radionova , proteolytic activity, and self-proliferative signaling. Galia B. Georgieva- Fetuin-A is a unique molecule which binds to the insulin Alexandrova, receptor, modulating its sensitivity, and transducing “the Alim V. Izmajlov physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inÀ ammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate Division of Biochemistry, with reduced glucose tolerance and insulin resistance. Medical University – Pleven, Impaired insulin sensitivity leads to the development of Bulgaria metabolic syndrome, an increased risk for type 2 diabetes 1Division of Medical Genetics, (T2DM), dyslipidaemias and cardiovascular diseases Medical University – Pleven, (CVDs). Furthermore, fetuin-A inversely correlates with Bulgaria inÀ ammatory and activation biomarkers, e.g. in patients with 2Repromed Medical Centrum – Pleven, T2DM. Thus, circulatory fetuin-A levels may have plausible Bulgaria predictive importance as a biomarker of risk of diabetes and 3Division of Pedagogy and Psychology, negative acute phase protein. Dysregulated, it plays a crucial Medical University – Pleven, role in the pathogenesis of some metabolic disorders and clinical inÀ ammatory conditions like metabolic syndrome, Bulgaria T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.
    [Show full text]
  • Soft Tissue Calcification in Mice Is Governed by Fetuin-A, Pyrophosphate and Magnesium
    bioRxiv preprint doi: https://doi.org/10.1101/577239; this version posted March 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Soft tissue calcification in mice is governed by fetuin-A, pyrophosphate and magnesium Anne Babler1*, Carlo Schmitz1*, Andrea Büscher1, Marietta Herrmann1,2, Felix Gremse3, Theo Gorgels4, Jürgen Floege5, Willi Jahnen-Dechent1 1 Helmholtz Institute for Biomedical Engineering, Biointerface Lab, RWTH Aachen University Hospital, Aachen, Germany 2 IZKF Research Group Tissue Regeneration in Musculoskeletal Regeneration, Orthopedic Center for Musculoskeletal Research, University of Würzburg, Würzburg, Germany 3 Helmholtz Institute for Biomedical Engineering, Experimental Molecular Imaging, RWTH Aachen University Hospital, Aachen, Germany 4 University Eye Clinic Maastricht, Maastricht University Medical Center, The Netherlands 5 Division of Nephrology and Clinical Immunology, RWTH Aachen University Hospital, Aachen, Germany *equal contribution Running title: Triple calcification inhibitor deficiency in Fetuin-A-Deficient DBA/2 Mice Corresponding author: Prof. Willi Jahnen-Dechent, Helmholtz Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen University Hospital, Pauwelsstrasse 30, 52074 Aachen, Germany, Phone: +49-241-8080163, Fax: +49-241-8082573, E-mail: willi.jahnen@rwth- aachen.de Keywords – calcification, mineral metabolism, fetuin-A, magnesium, pyrophosphate, mouse models Subject Codes - Animal Models of Human Disease, Fibrosis, Inflammation, Proteomics, Peripheral Vascular Disease Word count – XXXX (excl. References and Figure Legends) Total number of figures and tables – X figures, X tables, X supplement figures, X movies 1 bioRxiv preprint doi: https://doi.org/10.1101/577239; this version posted March 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder.
    [Show full text]
  • Mammalian Cell Growth Proteins, I. Growth Stimulation by Fetuin* by Theodore T
    MAMMALIAN CELL GROWTH PROTEINS, I. GROWTH STIMULATION BY FETUIN* BY THEODORE T. PUCK,t CHARLES A. WALDREN, AND CAROL JONES: UNIVERSITY OF COLORADO MEDICAL CENTER, DENVER Communicated October 30, 1967 In earlier papers we described the presence and properties of a factor in the fetuin fraction of fetal calf serum which promotes growth of mammalian cells in vitro and enhances their stretching on glass and other surfaces.1 Fetuin is an alpha-globulin, obtained by fractional precipitation with ammonium sulfate, whose major component is a glycoprotein of molecular weight 45,000.1 A synthetic medium was described which when supplemented with both albumin and fetuin produces virtually 100 per cent efficiency of colony growth of single HeLa cells plated in vitro.' Another synthetic medium, F12,2 was later developed in this laboratory which eliminated the need for albumin, greatly reduced the amount of fetuin required for maximal cell growth, and supported slow growth of some but not all cell strains without any protein supplement. Other laboratories have found or confirmed the presence of a growth-stimulating, alpha-globulin serum component,3 but questions have been raised as to whether the active fraction of fetal serum is indeed fetuin, and whether growth-promoting proteins from adult sera are similar to or different from those found in fetal sera.38' 4 The divergences of interpretation which have arisen are due to a variety of causes, including the presence of several components3 in the original fetuin described by Pedersen;6 the ease with which active fetuin preparations can lose their biological activity;" the lack of reliable, quantitative tests for titration of the biological activity of this growth-promoting factor; and the fact that various investigators have used different cells, media, and methodologies for assessment of the biological activities of their fractions.
    [Show full text]
  • The Role of Fetuin-A in Disease Processes Prevalent in Postmenopausal Women RETOS
    RETOS. Nuevas Tendencias en Educación Física, Deporte y Recreación ISSN: 1579-1726 [email protected] Federación Española de Docentes de Educación Física España Bane, Annie A.; Grandjean, Peter W. The Role of Fetuin-A in Disease Processes Prevalent in Postmenopausal Women RETOS. Nuevas Tendencias en Educación Física, Deporte y Recreación, núm. 27, enero- junio, 2015, pp. 172-179 Federación Española de Docentes de Educación Física Murcia, España Available in: http://www.redalyc.org/articulo.oa?id=345738764032 How to cite Complete issue Scientific Information System More information about this article Network of Scientific Journals from Latin America, the Caribbean, Spain and Portugal Journal's homepage in redalyc.org Non-profit academic project, developed under the open access initiative 2015, Retos, 27, 172-179 © Copyright: Federación Española de Asociaciones de Docentes de Educación Física (FEADEF) ISSN: Edición impresa: 1579-1726. Edición Web: 1988-2041 (www.retos.org) The Role of Fetuin-A in Disease Processes Prevalent in Postmenopausal Women El papel de la fetuina A en los procesos de enfermedad prevalentes en mujeres posmenopáusicas Annie A. Bane & Peter W. Grandjean Baylor University, USA Abstract. The purpose of this review is to summarize the role of fetuin-A in disease processes prevalent in postmenopausal women and synthesize effective interventions in obtaining healthy fetuin-A levels. A review of databases for articles related to fetuin-A and diseases associated with postmenopausal women was conducted. Articles were limited to full-text access, published in English since 1944. High fetuin-A levels are closely associated with decreased bone mineral density, increased cardiovascular disease risks, impairment of insulin signaling and disruption of adipocyte functioning.
    [Show full text]